Production of aminoaroylsulfonyl imides



United States Patent Ofi 3,340529-7 Patented Sept. 5, 1967 lce This invention concerns a process for the production of new aminoaroylsulfonyl imides which are obtained by reacting tertiary aromatic amines with sulfonyl isocyanates, and the new products obtained by the process.

It is known that sulfonyl imides are obtained by reacting a sulfonamide with an acyl chloride in the presence of a base. The yields obtained in this process are only moderate.

It is an object of this invention to provide a new process for the production of aminoaroylsulfonyl imides in which these substances are obtained in very good yields. A further object of this invention is to provide a process in which aminoaroylsulfonyl imides are obtained from the readily accessible starting materials.

I have found that aminoaroylsulfonyl imides of the formula R R Rx i i N CO-NH--S 02R;

Ra Ra I are obtained by reacting tertiary aromatic amines of the formula 1 R: R4 R1 /N --H R:

R R5 II with sulfonyl isocyanates of the formula OCNSO R HI in an inert organic solvent. In the formulae the groups R and R are cycloalkyl groups with 5 to 8 carbon atoms, arylalkyl groups with 7 to carbon atoms, alkyl groups with 1 to 6 carbon atoms, which may be substituted by an alkoxy group with l to 4 carbon atoms, a cyano group or a chlorine atom. The groups R and R may form a 5 to 6 membered saturated ring together with the nitrogen atom to which they are attached, and this ring may contain in addition an oxygen or sulfur atom. The groups R R R and R in the Formulae I and Hare hydrogen, alkyl with 1 to 4 carbon atoms, alkoxy with 1 to 4 carbon atoms, chlorine or bromine, while R is chlorine, alkyl with 1 to 6 carbon atoms, cycloalkyl with 5 to 8 carbon atoms or =aryl with 6 to 10 carbon atoms. The groups R and R may form a condensed benzene ring together with the carbon atoms to which they are attached. The groups R and R when taken together, may form a 5 or 6 membered heterocyclic ring containing the nitrogen atom to which R is attached, which ring can be condensed with a further 6 membered carbocyclic ring, such as a benzene or cyclohexane ring.

Stated alternatively, the above aminoaroylsul-fonyl imides in which R and R R and R and R and R are taken together have the respective formulae:

a I'll m R. NQ-C O-NH-S 0P3,

n; R, IV

N o O-NHS 02-12: R2

Ra Ra V Blow R4 {Q0 ONHS 02-31 R: I I

Ra Ra VI wherein R is a divalent, saturated group consisting of CH groups, and zero to one O- or S groups and forming with the N atom a 5-6 membered ring; R is a divalent hydrocarbon group forming a benzene ring with the two carbon to which R is attached; and R is a member from the group consisting of a divalent group forming a 5-6 membered heterocyclic ring with its N atom and a divalent group forming a 5-6 member heterocyclic ring with its N atom, said ring being condensed with a 6 carbon carbocyclic ring.

Stated alternatively, the corresponding tertiary aromatic amines have the respective formulae:

Ii N

l RI R5 V11 /N R: I

i Ru VIII and [\(RIDX R! i R: l I

R5 Ra IX wherein R R and R have the same meaning as defined above.

The reaction of amines of the Formula II with isocyanates of the Formula III was hitherto unknown. It dimethyl 'aniline and p-toluene sulfonyl isocyanate are used the reaction proceeds according to the following mechanism' Tertiary aromatic amines of the Formula II containing a hydrogen atom in the para-position to the amino group can be employed in the process described. Suitable substances are for example N,N-dimethylaniline, N,N-diethylaniline, N,N-di-n-butylaniline, N,N-isobutylaniline, N methyl N isobutylaniline, N ethyl N cyanoethylaniline, N ethyl N ethoxyethylaniline, N phenylpyrrolidine, N phenyl morpholine, N phenylthiomorpholine, N methyl 1,2,3,4 tetrahydroquinoline, N methylhexahydrocarbazole, N methyl N cyclohexylaniline, N ethyl N cyclooctylaniline, N,N dibenzylaniline, m dimethylaminoanisol, o chlorodiethylaniline, m dimethyltoluidine and a dimethylaminonaphthalene.

Chlorosulfonyl isocyanate, aliphatic or aromatic sulfonyl isocyanates may be used as isocyanates of the chlorosulfonyl isocyanate, ethanesulfonyl iscyanate,"n-

propylsulfonyl isocyanate, benzenesulfonyl isocyanate, ptoluenesulfonyl isocyanate and cyclohexylsulfonyl isocyanate. These substances can be readily produced by reacting phosgene or oxalyl chloridewith the corresponding sulfonamide.

Suitable inert organic solventsare those which do not react with isocyanate groups. Thushydrocarbons such as hexane, heptane, dodecane, benzene, toluene, xylene, cyclohexane and methylcyclohexane, and chlorinated hydrocarbons such as chloroform, carbon tetrachloride, 1,2- dichloroethane, chlorobenzene, oand m-dichlorobenzene and o-chlorotoluene may be employed. Ethers such as dibutyl ether and anisol may also be used as solvents.

In carrying out the process it is advantageous to use the starting material in a molar ratio of 1:1. .Anexcess of either of the-reaction partners may also beused, as for example up to 5 fold molar'excess. The process may be carried out at room temperature although it is preferably carried out at temperatures between 25 and 80 C. The reaction is exothermic so that it is often expedient to cool the reaction vessel during the reaction. The completion ofthe reaction is indicated, for example, by the fact that the temperature of the reaction mixture falls-without external cooling and by the disappearance of the isocyanate odor. The imide usually precipitates on completion of the reaction, on cooling the reaction mixture at the latest, and can be separated off by filtration or centrifugation. It is also possible to add-aqueous alkali tothe reaction mixture at room temperature'so that the imide goes into solution and can be precipitated with an acid such as hydrochloric acid if necessary after separation of undissolved material.

The aminoaroylsulfonyl imides obtained as described are valuable intermediates for the production of dyes and pharmaceuticals. The compounds themselves have a depressant effect on the blood sugar level. The corresponding p-aminobenzoic acids are obtained by boiling with aqueous alkali as for example with 2 N caustic soda. Thus p-dimethylaminobenzoic acid is obtained from pdirnethylaminobenzoyl-p toluenesulfonyl imide.

The quantities given in the examples are parts by Weight.

Example 1 20 parts benzene, 19.7 parts p-toluenesulfonyl isocyanate and 121 parts dimethylaniline are mixed at room are obtained. The compound melts at 19.9" to 200 C. after recrystallization from alcohol.

Example 2 219.7 parts p-toluenesulfonyl isocyanate are reacted with 14.9 parts diethylaniline as described in Example 1. 30.5

parts p-diethylaminobenzoylrp toluenesulfonyl imide of .the formula "are obtained. Thecompound melts at 180 to 130.5 0.

"after recrystallization from alcohol.

4 Example 3 19.7 parts p-toluenesulfonyl isocyanate are reacted with 20.5 parts di-n-butylaniline in the manner described. 39 parts crude p-di-n-butylaminobenzoyl-p-toluenesulfonyl imide of the formula 4 30 areobtained. The compound melts-at 161 to 163 C. after recrystallization from alcohol.

Example 4 58.5 parts p -toluenesulfonyl isocyanate are reacted with 44 parts N-phenylpyrrolidine by the method described in Example 1 in 65 partsbenzene. 92 parts crude p-pyrrolidinobenzoyl-p-toluenesulfonyl imide of the formula are obtained. The compound :melts at 274 'to 275 C.

with decomposition after recrystallization-from Y glacial acetic acid. Example 5 18.3 parts benzenesulfonyl isocyanate are reacted with 14.9 parts diethylaniline by the method described in Example 1. 25 parts p-diethylaminobenzoyl-benzenesulfonyl imide of the formula are obtained. The compound melts at 247 C. after recrystallization from dioxane.

Example 6 20.5 parts di-n-butylaniline in the manner described. 27 parts p-di-n-butylaminobenzoyl-benzenesulfonyl imide of the formula are obtained. The compound melts at 143 to 144 C. after recrystallization from alcohol.

Example 7 20 parts tosyl isocyanate, 17.5 parts N-ethyl-N-fl-cyanethylaniline and 16 parts benzene are heated for 6 hours at 40 C. The reaction product is filtered 01f and 14 parts crude p-(ethyl-fl cyanoethylamino)-benzoyl-p':toluenesulfonyl imide of the formula CgHs are obtained. The compound melts at 168 to. 170 C. after recrystallization from alcohol.

Example 8 20 parts tosyl isocyanate, 18.1 parts N-m-chloro-phenylpyrrolidine and .16 parts of benzene are reacted by the method described in- Example 7. 27 parts crude p-pyrrolidino-o-chlorobenzoyl-p'-toluenesulfonyl imide ofthe formula are obtained. The compound melts at 147 to 149 C. after recrystallization from alcohol.

Example 9 20 parts tosyl isocyanate, 18 parts N-di-n-propylaniline and 16 parts benzene are reacted by the method described in Example 1. 29 parts crude p-di-n-propylaminobenzoylp'-toluenesulfonyl imide of the formula are obtained. The compound melts at 147 to 149 C. after recrystallization from alcohol.

Example 10 20 parts tosyl isocyanate and 14 parts N-dimethyl-mtoluidine are reacted in 16 parts benzene by the method described in Example 1. 32 parts of a viscous crystalline material are obtained from which pure p-dimethylaminoo-toluyl-p'-toluenesulfonyl imide of the formula Cg; /NC O-NH-S 01-6-03, CH: l

are obtained by recrystallization from alcohol. The compound melts at 174 to 176 C.

Example 11 20 parts tosyl isocyanate, 27 parts dibenzylaniline and 16 parts benzene are mixed and heated under reflux for one hour. The reaction mixture is allowed to stand for two days and then filtered. 44 parts crude p-dibenzylaminobenzoyl-p'-toluenesulfonyl imide of the formula Cs r-C s are obtained. The compound melts at 168 to 170 C. after recrystallization from alcohol.

Example 12 20 parts tosyl isocyanate, 161 parts N-o-tolylpyrrolidine are reacted in 16 parts benzene as described in Example 1. 20 parts crude p-pyrrolidino-m-toluyl-p'-toluenesulfonyl imide of the formula ON aHMOP aH.

are obtained. The compound melts at 119 to 121 C. after recrystallization from alcohol.

Example 13 15.1 parts N-dimethyl-m-anisidine are reacted with 20 parts tosyl isocyanate in 16 parts benzene as described in Example 1. 23 parts crude p-dimethylamino-o-methoxybenzoyl-p'-toluenesulfonyl imide of the formula are obtained. The compound melts at 174 to 176 C. after recrystallization from dioxane.

Example 14 1 19 parts N-methyl-N-cyclohexylaniline are reacted with 20 parts tosyl isocyanate as described in Example 1. 30

- 6 parts crude p- (N-methyl-N-cyclohexylamino)-benzoyl-p'- toluenesulfonyl imide of the formula Ca u are obtained. The compound melts at 265 to 267 C. after recrystallization from ethylene glycol monomethyl ether.

Example 15 16.3 parts N-phenylmorpholine are reacted with 20 parts tosyl isocyanate as described in Example 1. 16 parts crude p-morpholinobenzoyl-p-toluenesulfonyl imide of the formula are obtained. The compound melts at 131 to 133 C. after recrystallization from benzene.

Example 17 20 parts tosyl isocyanate are reacted with 17.1 parts u-dimethylamino-naphthalene in benzene as described in Example 1. 27 parts of a crude imide which probably has the formula 0 ONH-SOz-CH:

are obtained. The compound melts at 198 to 198 C. after recrystallization from ethyl acetate.

Example 18 39 parts tosyl isocyanate and 38 parts N-methylhexahydrocarbazole are dissolved in 40 parts benzene. The reaction mixture is allowed to stand for several days and then filtered. 58 parts of a crude imide of the following formula 0 O-NH-S O:CH= H N I CH3 are obtained. The compound melts at 179 to 181 C.

Example 19 A solution of 14.2 parts chlorosulfonyl isocyanate in 10 parts benzene is added dropwise to a solution of 15 parts phenylpyrrolidine in 16 parts benzene at 20 C. The temperature rises to 50 C. An oily product is precipated which is insoluble in benzene and probably has the Example 20 6 parts dimethylaniline and 7.45 parts propane sulfonyl isocyanate are dissolved in parts benzene and heated on. V

aha

Examplell V i 7.45 parts diethylaniline and 7.45 parts propanesulfonyl isocyanate are heated in 60 parts benzene for two hoursat 40 C. The solution is concentrated in vacuo and the reaction product which separates out is pressed on a porous plate. 9 parts p-diethylamino-benzoylpropanesulfonyl imide are obtained. The compound melts at 175 to 176 C. after recrystallization from alcohol.

Example 22 8.4 parts dimethylaniline are reacted with 13 parts cyclohexylsulfonyl isocyanate in 30 parts benzene by the method described in Example 20. The p-di-methylamino-benzoyl-cyclohexylsulfony imide obtained melts at 194 to 196 C.

NQCo-NH-SOQ C 7 Example 23 p-Diethylamino-benzoyl-cyclohexylsulfonyl imide is obtained from 7.45 parts diethylaniline and 9.45 parts cyclohexylsulfonyl isocyanate by the method as described in Example 22. The product melts at 193 to 194 C. after recrystallization from alcohol.

I claim: 1. A process for the production of aminoaroylsulfonyl imides selected from the group consisting of imides of the formulae wherein R and R each denotes a member selected from the group consisting of cycloalkyl having 5 to 8 carbon. atoms, aralkyl having 7 to 10 carbon atoms, alkyl having 1 to 6 carbon atoms, alkyl having 1 to 6 carbon atoms substituted by an alkoxy group with 1 -to 4 carbon atoms, alkyl having 1 to 6 carbon atoms and substituted bya cyano group, and alkyl having 1 to 6 carbon atoms and substituted by chlorine, R R R and R each denotes a member selected from the group consisting of hydrogen, alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms, chlorine and bromine, R denotes a member selected from the group consisting of chlorine, alkyl having 1 to.6;carbon atoms, cycloalkyl having 5 to 8-carbon atoms and aryl .having 6 to 10 carbon atoms, wherein R is a divalent, saturated 'group consisting of --CH groups, and zeroto one -0 or S- groups and forming withN atom a-5-6 membered ring; R is a divalent hydrocarbon group forming a benzene ring with the two carbons to which R is attached; and R is a member from the group consisting of a divalent group forming a 5-6 membered heterocyclic ring with its N atom and a divalent group forming a' 5-6 member heterocyclic ring with its N atom, said ring being condensed with a 6 carbon carbocyli-c ring, which comprises reacting a tertiary aromatic .amine selected from the group consisting of an amine of the formula R3 R; Rr\

'Ra B5 II Ilia 4 Ra i N E Re I R R]\ f /N H R:

and low 4 N H wherein 1, 2, 3 4, 5, R6: 8 9 nd 1 have 111 meaning given above, with a sulfonyl isocyanate of the formula OCNAO -R 111 wherein R; has the meaning given above, in the presence of an inert organic solvent.

2. A process according to claim 1, wherein the reaction is carried out at a temperature between 25 and C. and said tertiary aromatic amine is N,N-dimethylaniline. I

3. A process for the production of p-aminobenzoylsulfonyl imides of the formula:

, a Rf a 11 wherein R and R have the respectivemeanings given 9 10 above with a sulfonyl isocyanate of the formula OTHER REFERENCES OCN-SO R wherein R has the meaning given above, in an inert, organic solvent. Seefelder, Matthias, Chemical Abstracts, Vol. 60, pages 4090-91, February (1964).

References Cited 5 FOREIGN PA ALEX MAZEL, Przmary Exammer.

902,881 8/1962 Great Britain. I. TOVAR, Assistant Examiner.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No 3 ,340 ,297 September 5 1967 Matthias Seefelder It is hereby certified that error appears in the above numbered patent requiring correction and that the said Letters Patent should read as corrected below.

Column 1, formula I, for that portion of the formula reading -C0-NI-I-SO R read CO-NHSO R column 5, line 1, for "147 to 149 C." read 178 to 180 C. column 6, lines 3 to 6, for that portion of the formula reading -CH read -CH line 23, for "19 parts" read 19.5 parts line 45, for "198 to 198 C." read 197 to 198 C line 67, for "precipated" read precipitated column 7, line 28, for "-cyc1ohexylsulfony" read -cyc1ohexy1sulfonyl Signed and sealed this 22nd day of April 1969.

(SEAL) Attest: I

EDWARD M.FLETCHER,JR. EDWARD J. BRENNER Attesting Officer Commissioner of Patents 

1. A PROCESS FOR THE PRODUCTION OF AMINOAROYLSULFONYL IMIDES SELECTED FROM THE GROUP CONSISTING OF IMIDES OF THE FORMULAE
 2. A PROCESS ACCORDING TO CLAIM 1, WHEREIN THE REACTION IS CARRIED OUT AT A TEMPERATURE BETWEEN 25 AND 80*C. AND SAID TERTIARY AROMATIC AMINE IS N,N-DIMETHYLANILINE. 